The present disclosure relates to a measuring probe, system, and method for non-invasive in vivo measurement of blood analytes by Raman spectroscopy.
For many applications it can be desirable to measure a concentration of blood analytes of a patient. For example, diabetic patients may benefit from a frequent measurement of glucose concentration in the blood to determine a state of health. However, traditional invasive measurements such as blood puncture and extraction can be stressful and painful over time and may give rise to health risks (e.g. infection). A non-invasive device for the measurement of blood analytes, such as glucose, is therefore desirable.
For example, international application WO 2011/083111 describes an apparatus for non-invasive in vivo measurement by Raman spectroscopy of glucose present in interstitial fluid in the skin of a subject. The apparatus comprises a measuring probe that receives light from a light source through a first fibre. The incoming light illuminates and interacts with the skin. Raman light received back from the skin, is collected by the probe and sent via a second fibre to a spectrometer connected to a computer for subsequent analysis of the spectral components. In the apparatus, optical components defining a return path for Raman scattered light selectively transmit light scattered from near a measurement location such that at least 50% of Raman scattered light received at the light detection unit originates at depths from 60 to 400 μm beyond a distal surface of the skin engaging probe. By the confocal configuration of the probe, the Raman light arises solely from interactions between the incoming light and the skin at the focus spot; hence contributions from the cone-like areas above and below the focus spot are minimized or eliminated.
For example, U.S. Pat. No. 7,873,397 describes another spectroscopic optical system for Raman spectroscopy to measure a blood and/or tissue analyte, wherein light that penetrates the target is collected from a region on the target's surface that is not directly illuminated. To this end, the collection optics preferably are placed directly in contact with the target or at least significantly close to the target. Light that illuminates the target is in a pattern that partially but not completely surrounds the region from which the portion of the light that penetrates the target is collected.
For example, US 2013/0018237 describes a different apparatus for non-invasive in vivo measurement by Raman spectroscopy wherein illumination light is focussed by a lens on the skin and Raman light is collected through the same lens. The Raman light is wavelength separated from the illumination light using a dichroic mirror.
For example, U.S. Pat. No. 8,515,506 describes methods for noninvasive determination of in vivo alcohol concentration using Raman spectroscopy. In the method, source and receiver fibres are placed against a tissue sampling surface.
Unfortunately, measurement of blood analyte concentrations by known, Raman-based reflection probes can be very sensitive to the exact positioning of the probe on the skin, thus making the known probes difficult to operate and less reproducible. Also, measurements by the known probes can lead to different results for different patients even when these patients have the same analyte concentration in their blood, thus requiring patient-specific calibration.
Accordingly, there is a desire for an improved measurement probe and system for non-invasive in vivo measurement of blood analytes by Raman spectroscopy that is easy to operate to provide reproducible results.